Genetic Variant CHI3L1:c.314+70G>C (chr1-203184506-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001276.4(CHI3L1):c.314+70G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,281,154 control chromosomes in the GnomAD database, including 157,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14582 hom., cov: 31)

Exomes 𝑓: 0.50 ( 143002 hom. )

Consequence

CHI3L1
NM_001276.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.310

Publications

17 publications found

Variant links:

Genes affected

CHI3L1 (HGNC:1932): (chitinase 3 like 1) Chitinases catalyze the hydrolysis of chitin, which is an abundant glycopolymer found in insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 family of chitinases includes eight human family members. This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling. [provided by RefSeq, Sep 2009]

CHI3L1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CHI3L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4 link	c.314+70G>C		intron_variant	Intron 4 of 9	ENST00000255409.8	NP_001267.2	P36222A0A024R969

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8 link	c.314+70G>C		intron_variant	Intron 4 of 9	1	NM_001276.4	ENSP00000255409.3		P36222

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63436

AN:

151796

Hom.:

14578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.420

GnomAD4 exome

AF:

0.497

AC:

561044

AN:

1129240

Hom.:

143002

AF XY:

0.498

AC XY:

287172

AN XY:

576902

show subpopulations

African (AFR)

AF:

0.222

AC:

5931

AN:

26752

American (AMR)

AF:

0.274

AC:

12064

AN:

44062

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

10488

AN:

23840

East Asian (EAS)

AF:

0.346

AC:

13158

AN:

38026

South Asian (SAS)

AF:

0.470

AC:

37181

AN:

79026

European-Finnish (FIN)

AF:

0.545

AC:

28888

AN:

53024

Middle Eastern (MID)

AF:

0.444

AC:

2274

AN:

5126

European-Non Finnish (NFE)

AF:

0.528

AC:

427959

AN:

809958

Other (OTH)

AF:

0.467

AC:

23101

AN:

49426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

13934

27869

41803

55738

69672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10380

20760

31140

41520

51900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.418

AC:

63465

AN:

151914

Hom.:

14582

Cov.:

AF XY:

0.419

AC XY:

31085

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.229

AC:

9479

AN:

41392

American (AMR)

AF:

0.345

AC:

5272

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1461

AN:

3466

East Asian (EAS)

AF:

0.347

AC:

1792

AN:

5158

South Asian (SAS)

AF:

0.478

AC:

2300

AN:

4814

European-Finnish (FIN)

AF:

0.552

AC:

5829

AN:

10552

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.526

AC:

35762

AN:

67934

Other (OTH)

AF:

0.419

AC:

883

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1774

3547

5321

7094

8868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.329

Hom.:

944

Bravo

AF:

0.389

Asia WGS

AF:

0.390

AC:

1360

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.71

(source)

DANN

Benign

0.66

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over